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Santa Barbara, CA, United States

Turner I.M.,Research Associate
Phytotaxa | Year: 2012

In his Natural Productions of Burma published in 1850, Francis Mason described a fig species that he referred to as the Tenasserim Banyan and legitimately published the name Ficus benjaminoides for it. This name has been very largely overlooked in the botanical literature. In the absence of type material, the name is here neotypifed to make F. benjaminoides Mason a synonym of Ficus benjamina. Mason's name makes Ficus benjaminoides Corner an illegitimate later homonym. © 2012 Magnolia Press. Source

New observations on various sauropod postcranial elements from Queensland provide insights into the taxonomic composition of northern Australia's sauropod fauna and the structure of sauropod vertebrae. An incomplete sauropod humerus from a site near Blackall, Queensland, represents the southernmost occurrence of sauropod fossils in the Eromanga Basin, and indicates a possibly new taxon. The internal architecture of at least one of the vertebral centra of Austrosaurus mckillopi comprises bony disks parallel to the posterior articular face and bony lamellae perpendicular to the anterior articular face reinforcing the structure against axial forces. The lack of pneumaticity proximally in dorsal ribs indicates that A. mckillopi may not be a titanosauriform. Material (QM F6737) from the Winton Formation includes probable osteoderms, the first known from Australian sauropods, and some of the oldest known. Comparison of this specimen with named Winton Formation sauropods suggests that it represents a distinct taxon. © 2011 Association of Australasian Palaeontologists. Source

Phorbol has long been considered a sort of "Holy Grail" for synthetic chemists, due to the inherent difficulty of assembling its large and complex structure and to its potential value as a basis for therapies. Phorbol-related compounds extracted from trees and shrubs such as the croton oil plant (Croton tiglium) are known as tiglianes and have powerful biological activity. They have been used by traditional societies for applications ranging from arrow poisons and purgatives to salves against skin cancer. Although phorbol and a few other tiglianes can be reliably obtained in large quantities from plant material, most compounds in this family have been essentially unobtainable by any means. The TSRI scientists' achievement, published in Nature on March 23, 2016, enables pharmaceutical researchers for the first time to make such tiglianes in the laboratory and evaluate them for possible development into drugs. "Ten years ago, synthetic chemists were thought to have no chance of making these compounds in useful quantities," said principal investigator Phil S. Baran, the Darlene Shiley Chair in Chemistry at TSRI. Other laboratories have previously succeeded in synthesizing phorbol, but via very burdensome and low-yield routes, which require between 40 and 52 steps and deliver the useless, structural mirror-image version of phorbol mixed with the desired form. These existing synthetic routes also cannot be modified easily to generate phorbol analogs (other structurally similar molecules). Pharmaceutical researchers rarely pursue the development of a promising compound if they have no way to look for better versions. The properties that make phorbol so hard to synthesize—its large, 20-carbon backbone structure and its six reactive oxygen atoms—are essentially the same ones that underlie its biological potency and therapeutic promise. Phorbol and other tiglianes interact with key signaling pathways in human cells and their patterns of oxygen atoms are in principle "tunable" to optimize them for a particular effect. "We like to think of the oxygen atoms that adorn these molecules as forming a sort of bar code," said Baran. "Their precise arrangement largely determines the molecule's function, so being able to make molecules with the desired arrangement is pretty important." One key to the new synthesis was a relatively simple strategy shift, which Baran and his colleagues first demonstrated in a study published in 2009, also in Nature. The targets then were eudesmanes, compounds that, like tiglianes, belong to the large class of chemicals known as terpenes. Baran's "two-phase terpene synthesis" approach involved broadly mimicking nature's ancient and flexible strategy by first building the carbon backbone, then adding the oxygen atoms. "Nature makes thousands of these terpenes in plant and animal cells, and within a family such as eudesmanes or phorbols the compounds don't differ much in their carbon skeleton—they're like the same car but with a different paint job and different wheels each time," said Baran. After the success with eudesmanes, Baran and his colleagues used the new approach again to find a short route to synthesizing ingenol, head of a family of more complex terpenes called ingenanes. That feat was reported in Science in 2013. One ingenane whose synthesis was made possible by the new route is currently being developed into a drug—and seems to have better properties than a plant-derived ingenane now used for treating precancerous skin lesions. Denmark-based LEO Pharmaceuticals, for which Baran did the ingenane work, later approached him for help concerning an even harder target: phorbol and the tiglianes. The company had identified a plant-derived tigliane as a promising skin cancer treatment, but had no way to generate improved analogs. Over 10 months, Baran and his team, including Research Associate Shuhei Kawamura, the new study's first author, used their two-phase, carbons-then-oxygens strategy to come up with the 19-step route to phorbol. The greatest difficulty involved the opening of a large part of the intermediate structure and installing of two separate oxygen-containing groups at one end of the molecule—a notorious challenge for would-be phorbol synthesizers. "If that reaction didn't work, we couldn't make the molecule," said Kawamura. The solution features one key step in which 13 different reactions occur in the same flask before yielding the desired intermediate product. "That transformation is the chemical equivalent of a Cirque du Soleil show," Baran said. As was the case for ingenol and the ingenanes, the new route can be modified easily to generate previously unobtainable tiglianes, in quantities sufficient for initial laboratory investigations. If needed, LEO Pharma could scale up the process to generate enough for preclinical tests in animals. In fact, the new route effectively starts from one of the intermediate products in the ingenol route, which the company is now able to supply in relatively large quantities. Baran emphasized that the new synthetic route to phorbol didn't require the invention of any novel reaction—all the reactions used had been previously described in the chemistry literature before 1980. "The whole pathway was enabled by just thinking differently about the overall strategy," he said. Explore further: Scientists find easier, cheaper way to make a sought-after chemical modification to drugs

News Article | April 7, 2016
Site: http://phys.org/biology-news/

Since the early 2000s when Research Associate Shawn Padgett pioneered the use of video cameras on nests to read bands, the Center for Conservation Biology (CCB) and other groups have used camera traps to identify breeding adult peregrine falcons.

News Article
Site: http://phys.org/biology-news/

iPSCs are derived from cells, usually taken from skin or blood, that have been genetically reprogrammed to revert back to an embryonic-like state, which enables the cells to differentiate into any cell type in the body. iPSC technology is a hugely important new platform for the study of human diseases in the laboratory, and, offers the potential to develop transformative cell replacement therapies, for example, by creating hepatic cells to treat liver disease and stem cells to treat leukaemia and other blood cancers. It is the ability of iPSCs to differentiate to other cell types that makes them so valuable for laboratory research, however not all iPSCs offer the same differentiation capacity, some cell lines are markedly defective. "When generating iPSCs it is clearly beneficial to identify 'good' and 'bad' cell lines" explains Dr Lee Stirling, who led the research team whilst a Research Associate at the UCL Cancer Institute. "Good cell lines offer optimal differentiation capacity and are therefore the most useful for research. However establishing the quality of these cell lines using traditional ways of assessment is costly and time-consuming. We were looking to find a way to expedite this process and we think part of the solution lies in using DNA methylation as a biomarker for differentiation capacity". DNA methylation is a physical modification to the genetic material (DNA) of a cell, which can alter the behaviour of that cell. In this study, the team were looking for a particular type of methylation that only occurs in stem cells, known as non-CG methylation, to see if they could identify a link between non-CG methylation and differentiation capacity of iPSCs. Dr Stirling says: "The role of a pluripotent stem cell is to generate all three germ layers: mesoderm, endoderm and ectoderm. These germ layers then develop into all cells of the body. For this study, we focussed specifically on a pluripotent stem cell's ability to differentiate into the endodermal lineage - the lineage for organs such as liver, pancreas and thyroid gland. Once we had collected and examined our data we were immediately struck by a link - we could confidently report that a reduction in non-CG methylation is associated with impaired differentiation capacity into endodermal lineages." "The main point of this study is that we have found an epigenetic biomarker that can help us distinguish iPSCs that have a diminished capacity for differentiation. This discovery can be used to reduce costly and time-consuming analysis methods, while simultaneously offering improvements in large-scale assessment of iPSC lines for clinical and therapeutic applications." adds Dr Stirling. The research team hope that not only will their discovery be used in the short-term as an efficient analysis method of cell lines for research purposes but, going forward, findings can be used as a starting point for discovering the developmental processes associated with methylation patterns in iPSCs. Dr Stirling concludes: "In time, I'm confident that understanding these principles will impact our understanding of cancer cell behaviour and, eventually, form a solid base for regenerative medicine strategies." This study was a collaboration between UCL, Cambridge University, Cellcentric and the Wellcome Trust Sanger Institute (HipSci). Explore further: Stem cell study could aid quest to combat range of diseases More information: Lee M. Butcher et al. Non-CG DNA methylation is a biomarker for assessing endodermal differentiation capacity in pluripotent stem cells, Nature Communications (2016). DOI: 10.1038/ncomms10458

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